TY - JOUR
T1 - A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth
AU - Rappoport, Nadav
AU - Toung, Jonathan
AU - Hadley, Dexter
AU - Wong, Ronald J.
AU - Fujioka, Kazumichi
AU - Reuter, Jason
AU - Abbott, Charles W.
AU - Oh, Sam
AU - Hu, Donglei
AU - Eng, Celeste
AU - Huntsman, Scott
AU - Bodian, Dale L.
AU - Niederhuber, John E.
AU - Hong, Xiumei
AU - Zhang, Ge
AU - Sikora-Wohfeld, Weronika
AU - Gignoux, Christopher R.
AU - Wang, Hui
AU - Oehlert, John
AU - Jelliffe-Pawlowski, Laura L.
AU - Gould, Jeffrey B.
AU - Darmstadt, Gary L.
AU - Wang, Xiaobin
AU - Bustamante, Carlos D.
AU - Snyder, Michael P.
AU - Ziv, Elad
AU - Patsopoulos, Nikolaos A.
AU - Muglia, Louis J.
AU - Burchard, Esteban
AU - Shaw, Gary M.
AU - O'Brodovich, Hugh M.
AU - Stevenson, David K.
AU - Butte, Atul J.
AU - Sirota, Marina
N1 - Funding Information:
This study was supported in part by March of Dimes Prematurity Research Center at Stanford, the Stanford Child Health Research Institute, and NIH (NHLBI) Grant 1RC2HL101748-01. Marina Sirota is supported by K01LM012381. The ITMI Cohort was supported by Inova Health System, and a generous gift of the Odeen family to ITMI. The GALA II study was supported in part by the National Heart Lung and Blood Institute R01 HL117004 and R01 HL104608, K12 HL119997, U01 OD019769, the National Institute of Health and Environmental Health Sciences R21ES24844, the Tobacco-Related Disease Research Program under Award Number 24RT-0025, the RWJF Amos Medical Faculty Development Award, the Sandler Foundation and the American Asthma Foundation to EGB, and the National Institute on Minority Health and Health Disparities under Award Number P60 MD006902, U54 MD009523 and R25 MD006832. The Boston Birth Cohort is supported in part by the March of Dimes PERI grants (20-FY02-56, #21-FY07-605, PI: Xiaobin Wang), and NIH grants (R21ES011666, R21HD066471, 2R01HD041702, PI: Xiaobin Wang). The content is solely the responsibility of the authors and does not necessarily represent the official views of the California Department of Public Health or the National Institutes of Health. Nikolaos A. Patsopoulos was support by a Career Independence Award from the National Multiple Sclerosis Society (TA 3056-A-2). We would like to thank David Hinds, Idit Kosti, Jieming Chen and Jeremy Pierce for useful discussion and insightful comments on the analysis.
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Preterm birth (PTB), or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. Although twin studies estimate that maternal genetic contributions account for approximately 30% of the incidence of PTB, and other studies reported fetal gene polymorphism association, to date no consistent associations have been identified. In this study, we performed the largest reported genome-wide association study analysis on 1,349 cases of PTB and 12,595 ancestry-matched controls from the focusing on genomic fetal signals. We tested over 2 million single nucleotide polymorphisms (SNPs) for associations with PTB across five subpopulations: African (AFR), the Americas (AMR), European, South Asian, and East Asian. We identified only two intergenic loci associated with PTB at a genome-wide level of significance: rs17591250 (P = 4.55E-09) on chromosome 1 in the AFR population and rs1979081 (P = 3.72E-08) on chromosome 8 in the AMR group. We have queried several existing replication cohorts and found no support of these associations. We conclude that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants, or of rare variants affected by environmental influences, all not detectable using a GWAS alone.
AB - Preterm birth (PTB), or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. Although twin studies estimate that maternal genetic contributions account for approximately 30% of the incidence of PTB, and other studies reported fetal gene polymorphism association, to date no consistent associations have been identified. In this study, we performed the largest reported genome-wide association study analysis on 1,349 cases of PTB and 12,595 ancestry-matched controls from the focusing on genomic fetal signals. We tested over 2 million single nucleotide polymorphisms (SNPs) for associations with PTB across five subpopulations: African (AFR), the Americas (AMR), European, South Asian, and East Asian. We identified only two intergenic loci associated with PTB at a genome-wide level of significance: rs17591250 (P = 4.55E-09) on chromosome 1 in the AFR population and rs1979081 (P = 3.72E-08) on chromosome 8 in the AMR group. We have queried several existing replication cohorts and found no support of these associations. We conclude that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants, or of rare variants affected by environmental influences, all not detectable using a GWAS alone.
UR - http://www.scopus.com/inward/record.url?scp=85040578611&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-18246-5
DO - 10.1038/s41598-017-18246-5
M3 - Article
C2 - 29317701
AN - SCOPUS:85040578611
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 226
ER -